CHEN 482 – Bioprocess Engineering

Dr. Ahmad K Hilaly

Artie McFerrin Department
of Chemical Engineering
Texas A&M University
 My background
• I have a PhD in Chemical Engineering
• 22 years of industrial experience
• Worked in the area of biopharmaceuticals, food,
feed, biofuels and renewable chemicals
• Scaled up processes from pilot plant to commercial
plant
• Held management positions
• R&D Director
• R&D manager
• Large scale separation experience
• Distillation
• Membrane
• Chromatography
• Ion Exchange
• Would like to enrich Chemical Engineering education
by bringing industrial perspectives in the classroom
 Text Book
• Textbook
– Bioprocess Engineering:Basic Concepts (Prentice Hall
International Series in the Physical and Chemical
Engineering Sciences) 3rd Edition by Michael Shuler,
Fikret Kargi, Matthew DeLisa
• Supplementary Book
– Bioprocess Engineering Principles, 2nd edition, Pauline
M. Doran
– Textbook is available online at:
http://ezproxy.library.tamu.edu/login?url=https://w
ww.sciencedirect.com/science/book/9780122208515
• Supplemental lecture notes on fundamentals
of Biology
 Office Hours
• My office hours:
– MW 3:30 pm – 5:00 pm (via Zoom)
– Join my Office Hours via Zoom at:
https://tamu.zoom.us/j/9058080834
• Teaching Assistant:
Name Email Office Hours Location

Siddhi Kotnis siddhi.kotnis@tamu.edu TBD TBD

 Grading

Midterm Exam 1 25%

Midterm Exam 2 25%
Final Exam 30%
Homework 15%
Quizzes 5%

Midterm Exam 1: September 28, 2021 in class (tentative)

Midterm Exam 2: November 2, 2021 in class (tentative)
Final Exam: University scheduled date/time.

Quizzes: approximately 1-3 weeks interval

 Guidelines for doing well

• Attend classes regularly

• Pay attention to lectures
• Take good notes
• Actively participate
• Review notes
• Do not fall behind
• Come to my office for additional help
 Expectations
• Exams will have both qualitative (T/F and multiple choice) questions and numerical
questions. It is expected that you remember the qualitative information presented
in the class
• It is expected that you review what you already learned in your Kinetics and Mass
Transfer classes
• Examples of solving numerical problems based on theories will be presented in
the class. You should not assume that the same problem with different parameters
will be in the exams.
• You are an engineer. It is expected that you understand the importance of
accuracy. If the required volume of a bioreactor is 1000 L and you use an equation
inappropriately to come up with an answer of 100 L, that will have significant
impact in real world situation.
• Please ask questions in the class to clarify an idea if you have not understood it
clearly.
• If you send me an email, please allow some time to receive my response. If your
questions are quite elaborate, it is expected that you discuss the questions with
me during my office hours.
• It is expected that you have tried your best on homework problems before you
seek help on homework
• Typically, I hold a short review at the beginning of each class. It is expected that
you actively participate in the review.
 Roadmap
End

1. Biomolecules
4 5
2. Enzymes
3. Cells
4. Metabolism
3 5. Genetics
6. Bioreactors
2 7. Bioseparations

1
Start
 Tentative Schedule
Week Tentative topic
1 Introduction and Syllabus
Case Study
2 Biomolecules
3 Enzyme kinetics
4 Enzyme kinetics
Cells
5 Cells
6 Stoichiometry
Bioenergetics
7 Metabolic Pathways
8 Genetics
9 Bioreactor design
10 Bioreactor design
11 Mass transfer
considerations
12 Mass transfer
considerations
13 Bioseparation
14 Bioseparation
 Bioprocess Engineering

What is Bioprocess Engineering?

“Bioprocess engineering is the sub-discipline within

biotechnology that is responsible for translating the
discoveries of life science into practical products,
processes, or systems that can serve the needs of
society”
(National Research Council)
 Challenges

• Biology is a vast field

• In addition to engineering calculations, you
will need to learn qualitative information
 Chemical Engineering

Chemistry

Chemical
Physics Math
Engineer

Economics
 Biochemical Engineering

Chemistry

Chemical
Physics Math
Engineer

Biology Economics
 Importance of Bioprocessing Industry
• Bioprocessing industry serves many sectors
– Pharmaceuticals
– Bio-pharmaceuticals
– Food
– Animal Feed
– Biofuels
– Biobased Chemicals
– Waste Treatment
– Petroleum production
Microbial enhanced oil recovery (MEOR)
 Industrial Bioproducts

• Organic Acids
• Alcohols
• Amino Acids
• Enzymes
• Bioplastics
• Antibiotics
• Biopharmaceuticals
• Nutraceuticals
Success Story of Commercial Production of Penicillin
 The Discovery

• In 1928 Alexander Fleming observed no bacterial growth on a Petri dish

near contaminating organism Penicillium notatum.
 The Process Development
• After a few years Howard Florey and Ernest Chain (Oxford
Professor) began working on developing a process
• In 1939 Howard Florey and Ernest Chain prepared a stable form of
penicillin from Penicillium chrysogenum that can be grown in
submerged culture and produced 200 times the amount from
Penicillium notatum.

Howard Ernest
Florey Chain
 The Engineering Challenges

What were the challenges of commercial production?

• Low rate of production

• Low concentration (~0.001 g/L)
• Low oxygen transfer rate
• Product instability

“I was ridiculed by some of my closest scientific friends for

allowing myself to become associated with what obviously
was to be a flop – namely, the commercial production of
penicillin by a fermentation process” (A.L. Elder)
 Developments
• Development of a corn steep liquor– lactose
medium which increased productivity ~10-fold
• Isolation of a better producer strain from a moldy
cantaloupe at a Peoria fruit market
• Manufacturing advances – “surface method”
where the mold was grown on the surface of liquid
in bottles
– High yield, but labor intensive
 Initial large scale Penicillin production method

Bottles used in penicillin production

Racks of bottles
 Developments

• Surface method could not meet demand and

a submerged tank process was developed
• Merck assigned an engineer and
microbiologist to work together on all
aspects of the problem – needs
interdisciplinary approach
• Over the years, such interactions have led to
remarkable increase in product
concentration, from 0.001 g/L to over 50 g/L
• Progress came from better understanding of
mold physiology, metabolism and genetics,
reactor design and control, and purification
 The Commercialization

• Merck, Pfizer, Squibb

• USDA Lab in Peoria, Illinois
• Pfizer built the first plant
• 14 fermenters 7000 gallons each
• US Production adequate to treat 100,000
patients per year by the end of WWII
Flow Diagram of Penicillin Production